Valine-derived phosphinothiourea as organocatalyst in enantioselective Morita–Baylis–Hillman reactions of acrylates with aromatic aldehydes

A new type of chiral bifunctional phosphinothiourea derived from l-valine is synthesized and used as an organocatalyst in the enantioselective Morita–Baylis–Hillman reaction of aromatic aldehydes with acrylates. The desired products were obtained in good enantioselectivities (up to 83% ee) and in excellent yields (up to 96%) under mild reaction conditions.

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(S)-1-(1-Diphenylphosphino3-methylbutan-2-yl)-3-phenylthioureaC24H27N2PS[α]D25=+32.1 (c 0.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(1-Diphenylphosphino-3-methylbutan-2-yl)-3-(4-methoxyphenyl)thioureaC25H29N2OPS[α]D25=+51.0 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(4-Chlorophenyl)-3-(1-diphenylphosphino-3-methylbutan-2-yl)thioureaC24H26ClN2PS[α]D25=+59.0 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(3,5-Bis(trifluoromethyl)phenyl)-3-(1-diphenylphosphino-3-methylbutan-2-yl)thioureaC26H25N2F6PS[α]D25=+7.0 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-Cyclohexyl-3-(1-diphenylphosphino-3-methylbutan-2-yl)thioureaC24H33N2PS[α]D25=-81.7 (c 0.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-1-(1-Diphenylphosphino-3-methylbutan-2-yl)-3-octylthioureaC26H39N2PS[α]D25=-11.0 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)